Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis

In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.     

The role of ethanol abuse in the etiology of heroin-related death

Toxicology analyses and other forensic science data were used to examine the mechanisms through which ethanol increased the risk for death caused by injected street preparations of heroin. The authors studied 505 victims of fatal heroin overdose and compared subjects who had concentrations of blood ethanol greater than 1000 mg/L (n = 306) with those who had concentrations less than, or equal to 1000 mg/L (n = 199). We found significant negative correlations between concentrations of ethanol and morphine (a heroin metabolite) in blood (R2 = 0.11, P = 0.0001 for log10-transformed variables) as well as between concentrations of blood ethanol and bile morphine (R2 = 0.16, P = 0.0001 for log10 bile morphine versus blood morphine). Toxicologic evidence of infrequent heroin use was more common in decedents with blood ethanol concentrations greater than 1000 mg/L than in those with lower concentrations. Our data suggest that ethanol enhances the acute toxicity of heroin, and that ethanol use indirectly influences fatal overdose through its association with infrequent (nonaddictive) heroin use and thus with reduced tolerance to the acute toxic effects of heroin.     

Heroin fatality due to penile injection

Death due to heroin overdose and/or rapid injection of heroin is a frequent occurrence among opioid addicts. We present an unusual case of heroin fatality due to the injection of the drug in the penis. Blood, urine, bile, and vitreous humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml, respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94 mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of death was determined to be due to heroin and ethanol intoxication.     

Drug contamination of US paper currency

It is known that US paper currency in the general circulation is contaminated with cocaine. Several mechanisms have been offered to explain this finding, including contamination due to handling during drug deals and the use of rolled up bills for snorting. Drug is then transferred from one contaminated bill to others during counting in financial institutions. The possibility of contamination of currency with other drugs has not been reported. In this study, the author reports the analysis of 10 randomly collected US$ 1 bills from five cities, for cocaine, heroin, 6-acetylmorphine (6-AM), morphine, codeine, methamphetamine, amphetamine and phencyclidine (PCP). Bills were immersed in acetonitrile for 2h prior to extraction and GC-MS analysis. Results showed that 92% of the bills were positive for cocaine with a mean amount of 28.75+/-139.07 microg per bill, a median of 1.37 microg per bill, and a range of 0.01-922.72 microg per bill. Heroin was detected in seven bills in amounts ranging from 0.03 to 168.50 microg per bill: 6-AM and morphine were detected in three bills; methamphetamine and amphetamine in three and one bills, respectively, and PCP was detected in two bills in amounts of 0.78 and 1.87 microg per bill. Codeine was not detected in any of the US$ 1 bills analyzed. This study demonstrated that although paper currency was most often contaminated with cocaine, other drugs of abuse may be detected in bills.     

Evaluation of the addiction history of a dead woman after exhumation and sectional hair testing.

In Greece, sectional hair analysis, in addition to clinical examination, has been used as a valuable tool for the confirmation of a person's history of drug use. The present report concerns the toxicologic analysis of the exhumed remains and hair samples of an 18-year-old woman. Postmortem toxicologic analysis of blood and urine confirmed recent opiate and cannabis use and indicated that death was associated with heroin abuse. Several months later, the woman's family asked for exhumation and reexamination of the body, insisting that the cause of death was homicide. The investigating judge ordered exhumation and new medicolegal examination of the body. The investigation of the drug profile along the hair shaft was undertaken by analyzing hair sections 1 cm from the hair root for morphine, 6-monoacetylmorphine, heroin, and cannabinoids. The total lengths of the hair samples ranged from 8 to 11 cm. The total morphine levels in the hair sections corresponding to the 3-month period before death were significantly lower (1.5-2.85 ng/mg) than those of the 4- to 10-month period before death (7.4-14.8 ng/mg). An interpretation of these results may be occasional drug use (with considerable attenuation of use during the last 3 months before death). Decrease of tolerance to heroin caused by abstinence and relapse in use could have been the cause of death.     

Fatal versus non-fatal heroin "overdose": blood morphine concentrations with fatal outcome in comparison to those of intoxicated drivers

The study was performed to distinguish fatal from non-fatal blood concentrations of morphine. For this purpose, blood levels of free morphine and total morphine (free morphine plus morphine conjugates) in 207 cases of heroin-related deaths were compared to those in 27 drivers surviving opiate intoxication. The majority of both survivors and non-survivors were found to show a concomitant use of depressants including alcohol or stimulants. Blood morphine levels in both groups varied widely, with a large area of overlap between survivors (free morphine: 0-128 ng/ml, total morphine: 10-2,110 ng/ml) and non-survivors (free morphine: 0-2,800 ng/ml, total morphine: 33-5,000 ng/ml). Five (18.5%) survivors and 87 (42.0%) non-survivors exhibit intoxication only by morphine. In these cases, too, both groups overlapped (survivors-free morphine: 28-93 ng/ml, total morphine: 230-1,451 ng/ml; non-survivors-free morphine: 0-2,800 ng/ml, total morphine: 119-4,660 ng/ml). Although the blood levels of free or total morphine do not allow a reliable prediction of survival versus non-survival, the ratio of free/total morphine may be a criterion to distinguish lethal versus survived intoxication. The mean of the ratio of free to total morphine for all lethal cases (N=207) was 0.293, for those that survived (N=27) 0.135, in cases of intoxication only by morphine 0.250 (N=87) and 0.080 (N=5), respectively. Applying a cut-off of 0.12 for free/total morphine and performing ROC analyses, fatal outcome can be predicted in 80% of the cases correctly, whereas 16% of the survivors were classified as dead. Nevertheless, in this study, all cases with a blood concentration of 200 ng/ml and more of free morphine displayed a fatal outcome.     

Role of alcohol in heroin overdose

The relationship between ethanol and risk of heroin overdosage was studied. Statistical processing of the results of forensic chemical analysis (460 expert evaluations) carried out in Chelyabinsk Regional Bureau of Forensic Medical Expert Evaluations in 2000 was carried out. The results of morphine and ethanol measurements in the blood and urine from corpses where deaths ensued from narcotic or ethanol poisoning, were analyzed. The concentrations of morphine in the blood and urine were measured on a gaseous chromatographer with mass-selective detector (Hewlett Packard HP 6890/HP-5972). Methods for measuring urinary and blood morphine are described. The results of statistical analysis demonstrated relationships between the age and ethanol concentrations in the blood and urine; blood ethanol and total urinary and blood morphine concentrations; blood concentration of free morphine and presence of 6-monoacetylmorphine in the blood. The authors conclude that the presence of ethanol in the blood together with morphine drastically augments the risk of rapid death from respiration arrest. It can also lead to a relatively high risk of overdosage in experienced narcomaniacs using heroin and ethanol.     

Morphine Concentrations in Stomach Contents of Intravenous Opioid Overdose Deaths

Abstract:  Death caused by heroin overdose is almost always the result of intravenous injection of the drug in Australia. We briefly describe a case where a heroin overdose was initially thought to be the result of oral ingestion of the drug, primarily as a result of higher concentrations of morphine in stomach contents than in blood. During the subsequent criminal trial and investigation, however, the issue of the entero-hepatic circulation of morphine was raised as a possible reason for the presence of morphine in the stomach contents. In this study, we report on the distribution of opioids in blood, stomach contents, urine, liver, and bile in 29 deaths caused by intravenous heroin overdose. The mean total and free blood morphine concentrations were 0.60 and 0.32 mg/L , respectively, and the mean stomach contents total morphine concentration was 1.16 mg/kg. All cases had detectable morphine in the stomach contents, and 24 of 29 cases (83%) had higher concentrations of total morphine in stomach contents than in blood. The mean total morphine concentration in bile was c. 100 times that in blood, and the liver total morphine concentration averaged twice that of blood levels. We conclude that the entero-hepatic circulation of morphine and subsequent reflux of duodenal contents back into the stomach can result in the deposition of morphine in gastric contents. Consequently, the relative levels of opioids in blood and stomach contents cannot be used to determine the site of administration of the drug.     

Fatal intoxication with tianeptine (Stablon)

Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of serotonin. A fatal case is presented involving a 26-year-old man, found lying in bed with a "mushroom of foam" around his mouth. Empty blister packs of Stablon and a suicide note were found next to the body. A liquid-liquid extraction procedure with n-hexane: ethyl acetate and n-hexane: 2-propanol, followed by LC-DAD-MS analysis, using positive mode electrospray ionization was performed. The detection limit was 0.001 microg/mL. The toxicological results revealed the following tianeptine concentrations in the post-mortem samples: blood 5.1 microg/mL; urine 2.0 microg/mL; liver 23 microg/g; stomach contents 22 mg. Femoral blood analyses also revealed an ethanol concentration of 0.53 g/L. The present method was also developed and validated for the other post-mortem specimens, since no previous published data had confirmed the post-mortem distribution of tianeptine. The absence of other suitable direct causes of death (macroscopic or histological) and the positive results achieved with the toxicological analysis led the pathologist to rule that death was due to an intoxication caused by the suicidal ingestion of tianeptine in combination with alcohol.     

An epidemic of illicit fentanyl deaths in Cook County, Illinois: September 2005 through April 2007

Between September 2005 and April 2007, 350 fentanyl intoxication deaths were investigated and certified by the Cook County Medical Examiners Office. Investigations revealed that the majority of these fatalities were by intravenous injection of a white powder followed by a rapid collapse. The fentanyl was clandestinely produced in a lab in Toluca, Mexico and sold by the Mickey Cobra street gang. The term "Drop Dead" was coined for this "tainted heroin." Postmortem samples were screened by ELISA and confirmed by standard GC-MS methods. Fentanyl fatalities peaked at 47 per month in May and June 2006. Fifty-two percent were single fentanyl intoxications, with the remainder accompanied by either cocaine, morphine from heroin, or alcohol. This epidemic stressed the limited resources of the toxicology laboratory and autopsy service of the Medical Examiners Office. The clandestine lab was terminated, distributing gang members and leaders arrested, and the epidemic ceased in April 2007.     

Drug deposition in adipose tissue and skin: evidence for an alternative source of positive sweat patch tests

In a series of licit and illicit drug-related deaths, qualitative and quantitative analyses on extracts of adipose tissue and skin were performed by GC/MS. In all cases, the adipose tissue was found to contain drugs at concentrations lower than, approximately equal to, or even greater than the concentrations of the same analytes found in the blood, which may reflect a consequence of long-term chronic exposure, or acute intoxication, or some combination of both. Approximately one cubic inch of skin with adipose tissue was removed from the mid to lower abdominal region adjacent to the midline incision during autopsy. The drugs were recovered from the specimens following incubation and alkaline, acidic, and alkaline chloroform back extraction of one to three grams of tissue. Deuterated analogs of the analytes were added to the matrix at the beginning of the incubation period. Cocaine and free morphine (from heroin) were readily identified in several cases. The presence of these illicit drugs in adipose tissue raises significant forensic questions, especially the use of 'sweat patches' to monitor recent cocaine or heroin use in chronic drug users.     

Dependence of acute opiate poisoning lethal outcome on the gender, age, and duration of addiction

The article presents toxicological characteristics of 198 cases of acute parenteral poisoning with morphine and heroin in the range of concentrations of their metabolites in the blood and urine which occur in practice. Risk of death is quantified in the range of possible morphine concentrations in the blood in acute opiates intoxication with reference to gender and age. Assessment of the criteria of quantitative opiates toxicity was made according to the method of logit regression and dose-effect curve suitable for analysis of correlations between probability of death and blood concentrations of opiates metabolites. Conditional lethal doses in respect to gender and age are calculated.     

尿样中海洛因代谢物的测定及海洛因滥用的确认

用ＳＰＥ－ＧＣ－ＮＰＤ法建立了尿样中吗啡、６－单乙酰吗啡及可待因的定性分析方法,适用于海洛因滥用者的尿样分析。尿样中吗啡及可待因的最小检测限均为５０ｎｇ／ｍｌ。方法的相对标准偏差分别为：吗啡１１．３％（ｎ＝５）,可待因１４．２％（ｎ＝５）。方法简便、灵敏、快速,１５ｍｉｎ可完成一例尿样的分析。研究了服用含可待因成分的复方甘草合剂后,尿样中的吗啡及可待因的峰面积比为０．４５７±０．１９７（Ｐ＝９９％）;统计了４０例明确滥用海洛因尿液的分析结果,吗啡与可待因的峰面积比为３．４６±０．８９４,Ｐ＝９９％。可作为判断海洛因滥用的依据。同时与免疫板法比较,附５５例免疫板法阳性尿样的分析结果     

High prevalence of 6-acetylmorphine in morphine-positive oral fluid specimens

Identification of 6-acetylmorphine, a specific metabolite of heroin, is considered to be definitive evidence of heroin use. Although 6-acetylmorphine has been identified in oral fluid following controlled heroin administration, no prevalence data is available for oral fluid specimens collected in the workplace. We evaluated the prevalence of positive test results for 6-acetylmorphine in 77,218 oral fluid specimens collected over a 10-month period (January-October 2001) from private workplace testing programs. Specimens were analyzed by Intercept immunoassay (cutoff concentration=30 ng/ml) and confirmed by GC-MS-MS (cutoff concentrations=30 ng/ml for morphine and codeine, and 3 ng/ml for 6-acetylmorphine). Only morphine-positive oral fluid specimens were tested by GC-MS-MS for 6-acetylmorphine. A total of 48 confirmed positive morphine results were identified. An additional 107 specimens were confirmed for codeine only. Of the 48 morphine-positive specimens, 32 (66.7%) specimens were positive for 6-acetylmorphine. Mean concentrations (+/-S.E.M.) of morphine, 6-acetylmorphine and codeine in the 32 specimens were 755+/-201, 416+/-168 and 196+/-36 ng/ml, respectively. Concentrations of 6-acetylmorphine in oral fluid ranged from 3 to 4095 ng/ml. The mean ratio (+/-S.E.M.) of 6-acetylmorphine/morphine was 0.33+/-0.06. It is suggested that, based on controlled dose studies of heroin administration, ratios >1 of 6-acetylmorphine/morphine in oral fluid are consistent with heroin use within the last hour before specimen collection. The confirmation of 6-acetylmorphine in 66.7% of morphine-positive oral fluid specimens indicates that oral fluid testing for opioids may offer advantages over urine in workplace drug testing programs and in testing drugged drivers for recent heroin use.     

Evaluation of certifier practices regarding alcohol-related deaths: Fulton County Medical Examiner's Center, Atlanta, Georgia, 2004

CONTEXT: Alcohol can contribute to various manners of death by acute intoxication that places a person at risk for fatal injury, acute fatal alcohol poisoning, or the various fatal complications of chronic abuse with or without superimposed acute intoxication. The reporting of alcohol use on the death certificate may vary with office policy or procedure, certifier judgment, and the timing of information received during investigation. OBJECTIVE: To determine the number of deaths including mention of alcohol use in the investigative case file, the number of death certificates on which alcohol use is reported, the number of discrepancies between the 2, and the possible reasons for observed discrepancies. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case review of all deaths where alcohol use was mentioned in the investigative case file and/or on the death certificate for deaths investigated by the Fulton County Medical Examiner in Atlanta, Georgia, during a 1-year period between January 1, 2004, and December 31, 2004. MAIN OUTCOME MEASURES: Percentage of deaths with alcohol use reported on the death certificate, tabulation of where and how alcohol use is reported on the death certificate, and tabulation of the differences between the investigative case file and death certificate regarding alcohol's possible role in causing death. RESULTS: Among the 1324 deaths certified by the office, 105 (8%) had alcohol use reported on the death certificate. The majority (67%) of these cases were natural deaths. Sixty-nine (5%) deaths had mention of alcohol use in the investigative case notes but did not include it on the death certificate. Twenty-five (2%) deaths had mention of alcohol on the death certificate but did not have mention of it in the investigative case file based on our search criteria. However, subsequent review of additional case follow-up information disclosed a history of alcohol use or acute intoxication in each case. CONCLUSIONS: The data show that more natural deaths are considered to be directly caused by alcohol than other manners of death. For the unnatural manners of death (excluding acute alcohol poisoning), alcohol use is often viewed by medical examiners as an incidental, associated finding or risk factor surrounding the circumstances of death rather than being an actual cause of death. In such cases, alcohol use is often omitted from the death certificate. For deaths directly caused by alcohol, the proportion of cases involving possible underreporting or overreporting of alcohol involvement was relatively small and usually involved the omission of chronic alcohol use from the death certificate. Researchers need to be aware of potential limitations of death certificate data for studying alcohol-related deaths.     

Distribution of dimethoate in the body after a fatal organophosphate intoxication

Many organophosphate pesticides (OPs) such as dimethoate are used to eradicate household pests, and those occurring in agriculture and forestry sectors. Combinations of two or more different insecticides have been manufactured to increase their effectiveness. A case of death is presented as suspected organophosphates intoxication. Autopsy was unremarkable except for grayish fluid in the stomach, with garlicky odor. A systematic toxicological analysis on post-mortem specimens revealed high concentrations of dimethoate in blood 38 microg/mL, urine 0.47 microg/mL, brain 2.2 microg/g, myocardial muscle 7.6 microg/g, liver 4.6 microg/g, lung 7.6 microg/g, skeletal muscle 21 microg/g, kidney 55 microg/g and gall bladder 31 microg/g. Blood alcohol was 2.85 g/L, cyclohexanone and cyclohexanol were also detected in the blood but not quantified. The cause of death was determined as organophosphate intoxication.     

Morphine and 6-acetylmorphine concentrations in blood, brain, spinal cord, bone marrow and bone after lethal acute or chronic diacetylmorphine administration to mice

The aim of this study was to evaluate postmortem incorporation of opiates in bone and bone marrow after diacetylmorphine (heroin) administration to mice. Mice were given acute (lethal dose of 300 mg/kg) or chronic (10 and 20 mg/kg/24 h for 20 days) intraperitoneal administration of diacetylmorphine. The two metabolites of diacetylmorphine, 6-acetylmorphine (6-AM) and morphine, were extracted from whole blood, brain, spinal cord, bone marrow and bone (after hydrolysis) using a liquid/liquid method. Quantification was performed by gas chromatography-mass spectrometry (GC/MS). Results showed that after acute administration, opiates were present in all studied tissues. Morphine concentrations appeared to be higher than those of 6-AM in blood (52.4 microg/mL versus 27.7 microg/mL, n=12), bone marrow (87.8 ng/mg versus 8.9 ng/mg, n=6) and bone (0.85 ng/mg versus 0.43 ng/mg, n=6), but 6-AM concentrations were higher than those of morphine in brain (14.0 ng/mg versus 7.4 ng/mg, n=12) and spinal cord (27.8 ng/mg versus 20.8 ng/mg, n=12). No correlation was found for both compounds between blood concentrations and either brain, spinal cord, bone or bone marrow concentrations while a significant one was found between brain and spinal cord concentrations either for morphine (r=0.89, n=12, p<0.001) or 6-AM (r=0.93, n=12, p<0.001), the concentration being higher in spinal cord than in brain. When bones were stored for 2 months, only 6-AM remained in bone marrow but not in bone. After chronic administration, mice being sacrificed by cervical dislocation 24 h after the last injection, no opiate was detected in any studied tissues. Further studies are required, in particular in human bones, but these results seem to show that 6-AM could be detect in bone marrow several weeks after the death and could be an alternative tissue for forensic toxicologist to detect a fatal diacetylmorphine overdose, even if no correlation between blood and bone marrow was observed. On the other hand, neither bone tissue nor bone marrow will allow the confirmation of a chronic diacetylmorphine use.     

Concentrations of free-morphine in peripheral blood after recent use of heroin in overdose deaths and in apprehended drivers

The concentration of free-morphine was determined in peripheral (femoral) blood from heroin-related deaths and compared with the concentration in venous blood from impaired drivers. The presence of 6-MAM in blood or urine served as a biomarker for recent use of heroin. Males dominated over females (p<0.001) in both the autopsy cases (88%) and the drivers (91%), although their mean age was about the same 33-35 y (p>0.05). Concentrations of free-morphine in blood were not associated with age of heroin users in Sweden (p>0.05). The median concentration of free-morphine was higher in autopsy cases (0.24 mg/L, N=766) compared with apprehended drivers with 6-MAM in blood (0.15 mg/L, N=124, p<0.05), and appreciably higher than in drivers with 6-MAM in urine but not in blood (0.03 mg/L, N=1823, p<0.001). The free-morphine concentration was above 0.20mg/L in 65% of autopsy cases, 36% of drivers with 6-MAM in blood but only 1.4% of drivers with 6-MAM in urine. Poly-drug deaths had about the same concentrations of free-morphine in blood (0.24 mg/L, N=703) as heroin-only deaths (0.25 mg/L, N=63). The concentration of morphine in drug overdose deaths (median 0.25 mg/L, N=669) was about the same as in traumatic deaths among heroin users (0.23 mg/L, N=97). However, the concentration of morphine was lower when the deceased had consumed alcohol (0.18 mg/L, N=104) compared with taking a benzodiazepine (0.32 mg/L, N=94). The concentration distributions of free-morphine in blood in heroin-related deaths overlapped with the concentrations in impaired drivers, which makes the interpretation of toxicology results difficult without knowledge about tolerance to opiates in any individual case.     

Detection of drugs of abuse in simultaneously collected oral fluid, urine and blood from Norwegian drug drivers

Blood and urine samples are collected when the Norwegian police apprehend a person suspected of driving under the influence of drugs other than alcohol. Impairment is judged from the findings in blood. In our routine samples, urine is analysed if morphine is detected in blood to differentiate between ingestion of heroin, morphine or codeine and also in cases where the amount of blood is too low to perform both screening and quantification analysis. In several cases, the collection of urine might be time consuming and challenging. The aim of this study was to investigate if drugs detected in blood were found in oral fluid and if interpretation of opiate findings in oral fluid is as conclusive as in urine. Blood, urine and oral fluid samples were collected from 100 drivers suspected of drugged driving. Oral fluid and blood were screened using LC-MS/MS methods and urine by immunological methods. Positive findings in blood and urine were confirmed with chromatographic methods. The analytical method for oral fluid included 25 of the most commonly abused drugs in Norway and some metabolites. The analysis showed a good correlation between the findings in urine and oral fluid for amphetamines, cocaine/benzoylecgonine, methadone, opiates, zopiclone and benzodiazepines including the 7-amino-benzodiazepines. Cocaine and the heroin marker 6-monoacetylmorphine (6-MAM) were more frequently detected in oral fluid than in urine. Drug concentrations above the cut-off values were found in both samples of oral fluid and urine in 15 of 22 cases positive for morphine, in 18 of 20 cases positive for codeine and in 19 of 26 cases positive for 6-MAM. The use of cannabis was confirmed by detecting THC in oral fluid and THC-COOH in urine. In 34 of 46 cases the use of cannabis was confirmed both in oral fluid and urine. The use of cannabis was confirmed by a positive finding in only urine in 11 cases and in only oral fluid in one case. All the drug groups detected in blood were also found in oral fluid. Since all relevant drugs detected in blood were possible to find in oral fluid and the interpretation of the opiate findings in oral fluid was more conclusive than in urine, oral fluid might replace urine in driving under the influence cases. The fast and easy sampling is time saving and less intrusive for the drivers.